tbuckley/cabot-search huggingface dataset:
SARS-CoV-2 infection induces a long-lived pro-inflammatory transcriptional profile
Authors: Jia-Yuan Zhang, Justin P. Whalley, Julian C. Knight, Linda S. Wicker, John A. Todd, Ricardo C. Ferreira
Journal: Genome Medicine (2023)

Abstract Background The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in COVID-19 patients has been extensively investigated. However, much less is known about the long-term effects of infection in patients and how it could affect the immune system and its capacity to respond to future perturbations. Methods Using a targeted single-cell multiomics approach, we have recently identified a prolonged anti-inflammatory gene expression signature in T and NK cells in type 1 diabetes patients treated with low-dose IL-2. Here, we investigated the dynamics of this signature in three independent cohorts of COVID-19 patients: (i) the Oxford COVID-19 Multi-omics Blood Atlas (COMBAT) dataset, a cross-sectional cohort including 77 COVID-19 patients and ten healthy donors; (ii) the INCOV dataset, consisting of 525 samples taken from 209 COVID-19 patients during and after infection; and (iii) a longitudinal dataset consisting of 269 whole-blood samples taken from 139 COVID-19 patients followed for a period of up to 7 months after the onset of symptoms using a bulk transcriptomic approach. Results We discovered that SARS-CoV-2 infection leads to a prolonged alteration of the gene expression profile of circulating T, B and NK cells and monocytes. Some of the genes affected were the same as those present in the IL-2-induced anti-inflammatory gene expression signature but were regulated in the opposite direction, implying a pro-inflammatory status. The altered transcriptional profile was detected in COVID-19 patients for at least 2 months after the onset of the disease symptoms but was not observed in response to influenza infection or sepsis. Gene network analysis suggested a central role for the transcriptional factor NF-κB in the regulation of the observed transcriptional alterations. Conclusions SARS-CoV-2 infection causes a prolonged increase in the pro-inflammatory transcriptional status that could predispose post-acute patients to the development of long-term health consequences, including autoimmune disease, reactivation of other viruses and disruption of the host immune system-microbiome ecosystem.
Combination of Rotarex Thrombectomy and Angioplasty in the Treatment of Aortic Endograft Occlusion
Authors: Weimin Li, Jinbao Qin, Kaichuang Ye, Lei Yuan, Minyi Yin, Weimin Li, Xiaoyu Wu, Xinrui Yang, Xinwu Lu
Journal: International Journal of Surgery (2023)

Objective: The aim of this retrospective single-center study was to assess the effectiveness and safety of Rotarex thrombectomy and angioplasty (balloon dilatation and stenting) in the treatment of aortic endograft occlusion (AEO) after the endovascular repair of abdominal aortic aneurysm (AAA). Methods: Among a total of 683 patients who underwent the endovascular aneurysm repair (EVAR) for AAA between May 2010 and March 2020, 46 (6.7%) patients developed occlusions of the aortic endograft; 16 patients were treated with fogarty embolectomy, 4 were treated with AngioJet aspiration, and 26 patients with mechanical thrombectomy (Rotarex system). The average time for AEO was 5 weeks (range 2-11 weeks). Immediately after angiography, Rotarex thrombectomy was used to remove the thrombus and embolus. After thrombectomy, balloon dilation was performed, followed by stent-graft deployment. The patients’ characteristics, treatment details, and outcomes were collected and analyzed. Results: There were 26 patients with AEO, 20 males (76.9%), and with the mean age of 67 ± 12 years (51-87). The primary reasons for AEO were kinking or extrinsic compression of the graft limb and thrombosis. The circulation was successfully restored in all patients by mechanical thrombectomy. Additional dilation/stents were required for 24 patients (93.3%), and they were placed in the graft limbs, thus re-establishing patency. The complications were observed in five patients and included peripheral embolization blue toe syndrome found in three patients and ischemia-reperfusion injury found in two patients. No mortality or recurrent thrombosis was observed in the follow-up period, which was extended for 12 months. Conclusions: The combination of Rotarex thrombectomy and angioplasty is a safe and effective treatment method for AEO after endovascular AAA repair.
Refining chimeric antigen receptors via barcoded protein domain combination pooled screening
Authors: Xavier Rios, Osmay Pardias, Marc A. Morales, Pradyot Bhattacharya, Yibin Chen, Linjie Guo, Chunchao Zhang, Erica J. Di Pierro, Gengwen Tian, Gabriel A. Barragan, Pavel Sumazin, Leonid S. Metelitsa
Journal: Molecular Therapy (2023)

Chimeric antigen receptor (CAR)-T cells represent a promising frontier in cancer immunotherapy. However, the current process for developing new CAR constructs is time consuming and inefficient. To address this challenge and expedite the evaluation and comparison of full-length CAR designs, we have devised a novel cloning strategy. This strategy involves the sequential assembly of individual CAR domains using blunt ligation, with each domain being assigned a unique DNA barcode. Applying this method, we successfully generated 360 CAR constructs that specifically target clinically validated tumor antigens CD19 and GD2. By quantifying changes in barcode frequencies through next-generation sequencing, we characterize CARs that best mediate proliferation and expansion of transduced T cells. The screening revealed a crucial role for the hinge domain in CAR functionality, with CD8a and IgG4 hinges having opposite effects in the surface expression, cytokine production, and antitumor activity in CD19- versus GD2-based CARs. Importantly, we discovered two novel CD19-CAR architectures containing the IgG4 hinge domain that mediate superior in vivo antitumor activity compared with the construct used in Kymriah, a U.S. Food and Drug Administration (FDA)-approved therapy. This novel screening approach represents a major advance in CAR engineering, enabling accelerated development of cell-based cancer immunotherapies.
Advancements in computer-assisted diagnosis of Alzheimer's disease: A comprehensive survey of neuroimaging methods and AI techniques for early detection
Authors: Kogilavani Shanmugavadivel, V.E. Sathishkumar, Jaehyuk Cho, Malliga Subramanian
Journal: Ageing Research Reviews (2023)

Alzheimer's Disease (AD) is a brain disorder that causes the brain to shrink and eventually causes brain cells to die. This neurological condition progressively hampers cognitive and memory functions, along with the ability to carry out fundamental tasks over time. From the symptoms it is very difficult to detect during its early stage. It has become necessary to develop a computer assisted diagnostic models for the early AD detection. This survey work, discussed about a review of 110 published AD detection methods and techniques from the year 2011 to till-date. This study lies in its comprehensive exploration of AD detection methods using a range of artificial intelligence (AI) techniques and neuroimaging modalities. By collecting and analysing 50 papers related to AD diagnosis datasets, the study provides a comprehensive understanding of the diversity of input types, subjects, and classes used in AD research. Summarizing 60 papers on methodologies gives researchers a succinct overview of various approaches that contribute to enhancing detection accuracy. From the review, data are acquired and pre-processed form multiple modalities of neuroimaging. This paper mainly focused on review of different datasets used, various feature extraction methods, parameters used in neuro images. To diagnosis the Alzheimer's disease, the existing methods utilized three most common artificial intelligence techniques such as machine learning, deep learning, and transfer learning. We conclude this survey work by providing future perspectives for AD diagnosis at early stage.
Myelodysplasia after clonal hematopoiesis with APOBEC3-mediated CYBB inactivation in retroviral gene therapy for X-CGD
Authors: Toru Uchiyama, Toshinao Kawai, Kazuhiko Nakabayashi, Yumiko Nakazawa, Fumihiro Goto, Kohji Okamura, Toyoki Nishimura, Koji Kato, Nobuyuki Watanabe, Akane Miura, Toru Yasuda, Yukiko Ando, Tomoko Minegishi, Kaori Edasawa, Marika Shimura, Yumi Akiba, Aiko Sato-Otsubo, Tomoyuki Mizukami, Motohiro Kato, Koichi Akashi, Hiroyuki Nunoi, Masafumi Onodera
Journal: Molecular Therapy (2023)
Hormesis defines the limits of lifespan
Authors: Edward J. Calabrese, Naomi Osakabe, Rosanna Di Paola, Rosalba Siracusa, Roberta Fusco, Ramona D’Amico, Daniela Impellizzeri, Salvatore Cuzzocrea, Tilman Fritsch, Ali S. Abdelhameed, Uwe Wenzel, Claudio Franceschi, Vittorio Calabrese
Journal: Ageing Research Reviews (2023)

This commentary provides a novel synthesis of how biological systems adapt to a broad spectrum of environmental and age-related stresses that are underlying causes of numerous degenerative diseases and debilitating effects of aging. It proposes that the most fundamental, evolutionary-based integrative strategy to sustain and protect health is based on the concept of hormesis. This concept integrates anti-oxidant, anti-inflammatory and cellular repair responses at all levels of biological organization (i.e., cell, organ and organism) within the framework of biphasic dose responses that describe the quantitative limits of biological plasticity in all cells and organisms from bacteria and plants to humans. A major feature of the hormetic concept is that low levels of biological, chemical, physical and psychological stress upregulate adaptive responses that not only precondition, repair and restore normal functions to damaged tissues/organs but modestly overcompensate, reducing ongoing background damage, thereby enhancing health beyond that in control groups, lacking the low level "beneficial" stress. Higher doses of such stress often become counterproductive and eventually harmful. Hormesis is active throughout the life-cycle and can be diminished by aging processes affecting the onset and severity of debilitating conditions/diseases, especially in elderly subjects. The most significant feature of the hormetic dose response is that the limits of biological plasticity for adaptive processes are less than twice that of control group responses, with most, at maximum, being 30-60 % greater than control group values. Yet, these modest increases can make the difference between health or disease and living or dying. The quantitative features of these adaptive hormetic dose responses are also independent of mechanism. These features of the hormetic dose response determine the capacity to which systems can adapt/be protected, the extent to which biological performance (e.g., memory, resistance to injury/disease, wound healing, hair growth or lifespan) can be enhanced/extended and the extent to which synergistic interactions may occur. Hormesis defines the quantitative rules within which adaptive processes operate and is central to evolution and biology and should become transformational for experimental concepts and study design strategies, public health practices and a vast range of therapeutic strategies and interventions.
A machine learning-based choledocholithiasis prediction tool to improve ERCP decision making: a proof-of-concept study
Authors: Steven N. Steinway, Bohao Tang, Brian S. Caffo, Venkata S. Akshintala, Jeremy Telezing, Aditya Ashok, Ayesha Kamal, Chung Yao Yu, Nitin Jagtap, James L. Buxbaum, Joseph Elmunzer, Sachin B. Wani, Mouen A. Khashab
Journal: Endoscopy (2023)

Abstract Background Previous studies demonstrated limited accuracy of existing guidelines for predicting choledocholithiasis, leading to overutilization of endoscopic retrograde cholangiopancreatography (ERCP). More accurate stratification may improve patient selection for ERCP and allow use of lower-risk modalities. Methods A machine learning model was developed using patient information from two published cohort studies that evaluated performance of guidelines in predicting choledocholithiasis. Prediction models were developed using the gradient boosting model (GBM) machine learning method. GBM performance was evaluated using 10-fold cross-validation and area under the receiver operating characteristic curve (AUC). Important predictors of choledocholithiasis were identified based on relative importance in the GBM. Results 1378 patients (mean age 43.3 years; 61.2% female) were included in the GBM and 59.4% had choledocholithiasis. Eight variables were identified as predictors of choledocholithiasis. The GBM had accuracy of 71.5% (SD 2.5%) (AUC 0.79 [SD 0.06]) and performed better than the 2019 American Society for Gastrointestinal Endoscopy (ASGE) guidelines (accuracy 62.4% [SD 2.6%]; AUC 0.63 [SD 0.03]) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines (accuracy 62.8% [SD 2.6%]; AUC 0.67 [SD 0.02]). The GBM correctly categorized 22% of patients directed to unnecessary ERCP by ASGE guidelines, and appropriately recommended as the next management step 48% of ERCPs incorrectly rejected by ESGE guidelines. Conclusions A machine learning-based tool was created, providing real-time, personalized, objective probability of choledocholithiasis and ERCP recommendations. This more accurately directed ERCP use than existing ASGE and ESGE guidelines, and has the potential to reduce morbidity associated with ERCP or missed choledocholithiasis.
Impact of low disease activity, remission, and complete remission on flares following tapering of corticosteroids and immunosuppressive therapy in patients with systemic lupus erythematous: a multinational cohort study
Authors: Jiacai Cho, Liang Shen, Molla Huq, Rangi Kandane-Rathnayake, Vera Golder, Worawit Louthrenoo, Yi-Hsing Chen, Laniyati Hamijoyo, Shue-Fen Luo, Yeong-Jian J Wu, Leonid Zamora, Zhanguo Li, Sargunan Sockalingam, Yasuhiro Katsumata, Masayoshi Harigai, Yanjie Hao, Zhuoli Zhang, Duminda Basnayake, Madelynn Chan, Jun Kikuchi, Tsutomu Takeuchi, Sang-Cheol Bae, Shereen Oon, Sean O'Neill, Fiona Goldblatt, Kristine Pek Ling Ng, Annie Law, Nicola Tugnet, Sunil Kumar, Cherica Tee, Michael Tee, Naoaki Ohkubo, Yoshiya Tanaka, Sandra V Navarra, Chak Sing Lau, Alberta Hoi, Eric F Morand, Mandana Nikpour, Aisha Lateef
Journal: The Lancet Rheumatology (2023)
Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial
Authors: Fred Saad, Noel W Clarke, Mototsugu Oya, Neal Shore, Giuseppe Procopio, João Daniel Guedes, Cagatay Arslan, Niven Mehra, Francis Parnis, Emma Brown, Friederike Schlürmann, Jae Young Joung, Mikio Sugimoto, Oliver Sartor, Yu-Zhen Liu, Christian Poehlein, Laura Barker, Paula Michelle del Rosario, Andrew J Armstrong
Journal: The Lancet Oncology (2023)
Hemostasis defects underlying the hemorrhagic syndrome caused by mammarenaviruses in a cynomolgus macaque model
Authors: Blaise Lafoux, Nicolas Baillet, Caroline Picard, Gustave Fourcaud, Virginie Borges-Cardoso, Stéphanie Reynard, Alexandra Journeaux, Clara Germain, Emeline Perthame, Mathieu Mateo, Jimmy Hortion, Xavier Carnec, Natalia Pietrosemoli, Marie Moroso, Orianne Lacroix, Ophélie Jourjon, Stéphane Barron, Audrey Vallve, Aurélie Duthey, Frédéric Jacquot, Laura Barrot, Manon Dirheimer, Hervé Raoul, Christophe Nougier, Sylvain Baize
Journal: Blood (2023)
Brain tumor-related epilepsy management: A Society for Neuro-oncology (SNO) consensus review on current management
Authors: Edward K Avila, Steven Tobochnik, Sara K Inati, Johan A F Koekkoek, Guy M McKhann, James J Riviello, Roberta Rudà, David Schiff, William O Tatum, Jessica W Templer, Michael Weller, Patrick Y Wen
Journal: Neuro-Oncology (2023)

Abstract Tumor-related epilepsy (TRE) is a frequent and major consequence of brain tumors. Management of TRE is required throughout the course of disease and a deep understanding of diagnosis and treatment is key to improving quality of life. Gross total resection is favored from both an oncologic and epilepsy perspective. Shared mechanisms of tumor growth and epilepsy exist, and emerging data will provide better targeted therapy options. Initial treatment with antiseizure medications (ASM) in conjunction with surgery and/or chemoradiotherapy is typical. The first choice of ASM is critical to optimize seizure control and tolerability considering the effects of the tumor itself. These agents carry a potential for drug–drug interactions and therefore knowledge of mechanisms of action and interactions is needed. A review of adverse effects is necessary to guide ASM adjustments and decision-making. This review highlights the essential aspects of diagnosis and treatment of TRE with ASMs, surgery, chemotherapy, and radiotherapy while indicating areas of uncertainty. Future studies should consider the use of a standardized method of seizure tracking and incorporating seizure outcomes as a primary endpoint of tumor treatment trials.
HLA-DRB1 and HLA-DQA1 associated with immunogenicity to adalimumab therapy in patients with rheumatoid arthritis
Authors: Chuan Fu Yap, Nisha Nair, Annick de Vries, Floris C Loeff, Ann W Morgan, John D Isaacs, Anthony G Wilson, Kimme L Hyrich, Anne Barton, Darren Plant
Journal: Annals of the Rheumatic Diseases (2023)

Comparison within patients with complete MTX information, those with missing information were not included in this analysis.†Comparison within recorded patients of having known combination therapy, as well as complete MTX information.‡Ever smoker refers to ex smokers and current smokers.ACPA, anti-citrullinated peptide antibody; ADA,
Exploring the pain and disability continuum in adolescents with non-traumatic anterior knee pain: a mediation analysis using individual participant data of prospective studies
Authors: Sinead Holden, Hopin Lee, Marienke van Middelkoop, Michael Skovdal Rathleff
Journal: British Journal of Sports Medicine (2023)

Objective To use individual patient data (IPD) to investigate if the effect of pain on sports-related disability is mediated through physical (lower extremity isometric strength) or psychological (depression/anxiety and knee confidence) factors in adolescents with non-traumatic anterior knee pain. Methods This study included four datasets from a previously harmonised IPD dataset. Prior to analysis, the protocol and analysis approach were predefined and published on Open Science Framework. Potential mediators were pre-sepcified as isometric knee and hip strengths, self-reported anxiety/depression and confidence in the knee, all measured at 12 weeks after baseline evaluation. Mediation analyses were undertaken using the CMAVerse package in RStudio using the regression-based approach to decompose the total effect of the exposure (pain at baseline evaluation) on the outcome (sports-related disability at 6 months) into the ‘indirect effect’ (the portion of the total effect acting through the mediators) and the ‘direct effect’. Results Two-hundred and seventy-nine adolescents with non-traumatic knee pain were included in the analysis. Median age was 13 (range 10–19), and 72% were women. Baseline pain was associated with sports-related disability at 6 months. There was no evidence of the association being mediated by any of the proposed mediators (total natural indirect effect for strength 0.01 (−1.14 to 1.80) and psychological factors 0.00 (−0.66 to 2.02)). Conclusion We found an effect of pain on sports-related disability at 6 months which appears to be independent of lower extremity muscle strength, or depression/anxiety and knee confidence in adolescents with non-traumatic anterior knee pain.
CD7 targeted “off-the-shelf” CAR-T demonstrates robust in vivo expansion and high efficacy in the treatment of patients with relapsed and refractory T cell malignancies
Authors: Shiqi Li, Xinxin Wang, Lin Liu, Jia Liu, Jun Rao, Zhongtao Yuan, Li Gao, Yu Li, Le Luo, Gui Li, Zhimin Li, Sheng Li, Jiaping He, Lihua Zhang, Lvzhe Chen, Wenhui Huang, Ping Yin, Chunmin Li, Xiaoping Li, Youcheng Wang, Yancheng Dong, Dingsong Zhang, Qingying Zang, Yingnian Chen, Lianjun Shen, Wenling Li, Wei Cao, Xi Zhang, Sanbin Wang
Journal: Leukemia (2023)
Considerations for addressing bias in artificial intelligence for health equity
Authors: Michael D. Abràmoff, Michelle E. Tarver, Nilsa Loyo-Berrios, Sylvia Trujillo, Danton Char, Ziad Obermeyer, Malvina B. Eydelman, William H. Maisel
Journal: npj Digital Medicine (2023)

Abstract Health equity is a primary goal of healthcare stakeholders: patients and their advocacy groups, clinicians, other providers and their professional societies, bioethicists, payors and value based care organizations, regulatory agencies, legislators, and creators of artificial intelligence/machine learning (AI/ML)-enabled medical devices. Lack of equitable access to diagnosis and treatment may be improved through new digital health technologies, especially AI/ML, but these may also exacerbate disparities, depending on how bias is addressed. We propose an expanded Total Product Lifecycle (TPLC) framework for healthcare AI/ML, describing the sources and impacts of undesirable bias in AI/ML systems in each phase, how these can be analyzed using appropriate metrics, and how they can be potentially mitigated. The goal of these “Considerations” is to educate stakeholders on how potential AI/ML bias may impact healthcare outcomes and how to identify and mitigate inequities; to initiate a discussion between stakeholders on these issues, in order to ensure health equity along the expanded AI/ML TPLC framework, and ultimately, better health outcomes for all.
Alzheimer’s disease as a viral disease: Revisiting the infectious hypothesis
Authors: Francesco Bruno, Paolo Abondio, Rossella Bruno, Leognano Ceraudo, Ersilia Paparazzo, Luigi Citrigno, Donata Luiselli, Amalia C. Bruni, Giuseppe Passarino, Rosanna Colao, Raffaele Maletta, Alberto Montesanto
Journal: Ageing Research Reviews (2023)

Alzheimer's disease (AD) represents the most frequent type of dementia in elderly people. Two major forms of the disease exist: sporadic - the causes of which have not yet been fully understood - and familial - inherited within families from generation to generation, with a clear autosomal dominant transmission of mutations in Presenilin 1 (PSEN1), 2 (PSEN2) or Amyloid Precursors Protein (APP) genes. The main hallmark of AD consists of extracellular deposits of amyloid-beta (Aβ) peptide and intracellular deposits of the hyperphosphorylated form of the tau protein. An ever-growing body of research supports the viral infectious hypothesis of sporadic forms of AD. In particular, it has been shown that several herpes viruses (i.e., HHV-1, HHV-2, HHV-3 or varicella zoster virus, HHV-4 or Epstein Barr virus, HHV-5 or cytomegalovirus, HHV-6A and B, HHV-7), flaviviruses (i.e., Zika virus, Dengue fever virus, Japanese encephalitis virus) as well as Human Immunodeficiency Virus (HIV), hepatitis viruses (HAV, HBV, HCV, HDV, HEV), SARS-CoV2, Ljungan virus (LV), Influenza A virus and Borna disease virus, could increase the risk of AD. Here, we summarized and discussed these results. Based on these findings, significant issues for future studies are also put forward.